Objectives: In March 2023, an alternative school in the Republic of Korea reported 12 cases of shigellosis. This study aims to analyze the epidemiological characteristics in order to determine the cause of the cluster outbreak of shigellosis and to develop prevention strategies. Methods: This study focused on 12 patients with confirmed Shigella infection and investigated their demographics, clinical features, epidemiology, diagnostics, and antimicrobial susceptibility. Following the identification of Shigella, we conducted follow-up rectal smear cultures to manage patients, implementing isolation and control measures. Results: This study investigated the emergence of multidrug-resistant Shigella following missionary activities in Cambodia, documenting a cluster infection within an alternative school in Daejeon, the Republic of Korea. The outbreak affected 56 participants, resulting in the confirmation of 12 cases. The incidence rates varied by gender and occupation, with higher rates among males and teachers. All 12 cases demonstrated multidrug resistance. Challenges included delayed pathogen confirmation and suboptimal adherence to isolation criteria. The incident prompted revisions in the criteria for isolation release, focusing on symptom resolution. The study underscores the necessity for strengthened surveillance, educational initiatives focusing on prevention in endemic areas, and improved oversight of unlicensed educational establishments. Conclusion Successful response strategies included swift situation assessment, collaborative efforts, effective infection control measures, and modified criteria for isolation release. Continued surveillance of multidrug-resistant strains is recommended, especially in regions with a high prevalence.